Hotspots for Initiation of Meiotic Recombination.

Homologous chromosomes must pair and recombine to ensure faithful chromosome segregation during meiosis, a specialized type of cell division that occurs in sexually reproducing eukaryotes. Meiotic recombination initiates by programmed induction of DNA double-strand breaks (DSBs) by the conserved type II topoisomerase-like enzyme SPO11. A subset of meiotic DSBs are resolved as crossovers, whereby reciprocal exchange of DNA occurs between homologous chromosomes. Importantly, DSBs are non-randomly distributed along eukaryotic chromosomes, forming preferentially in permissive regions known as hotspots. In many species, including plants, DSB hotspots are located within nucleosome-depleted regions. DSB localization is governed by interconnected factors, including cis-regulatory elements, transcription factor binding, and chromatin accessibility, as well as by higher-order chromosome architecture. The spatiotemporal control of DSB formation occurs within a specialized chromosomal structure characterized by sister chromatids organized into linear arrays of chromatin loops that are anchored to a proteinaceous axis. Although SPO11 and its partner proteins required for DSB formation are bound to the axis, DSBs occur preferentially within the chromatin loops, which supports the "tethered-loop/axis model" for meiotic recombination. In this mini review, we discuss insights gained from recent efforts to define and profile DSB hotspots at high resolution in eukaryotic genomes. These advances are deepening our understanding of how meiotic recombination shapes genetic diversity and genome evolution in diverse species

Hotspots for Initiation of Meiotic Recombination

Homologous chromosomes must pair and recombine to ensure faithful chromosome segregation during meiosis, a specialized type of cell division that occurs in sexually reproducing eukaryotes. Meiotic recombination initiates by programmed induction of DNA double-strand breaks (DSBs) by the conserved type II topoisomerase-like enzyme SPO11. A subset of meiotic DSBs are resolved as crossovers, whereby reciprocal exchange of DNA occurs between homologous chromosomes. Importantly, DSBs are non-randomly distributed along eukaryotic chromosomes, forming preferentially in permissive regions known as hotspots. In many species, including plants, DSB hotspots are located within nucleosome-depleted regions. DSB localization is governed by interconnected factors, including cis-regulatory elements, transcription factor binding, and chromatin accessibility, as well as by higher-order chromosome architecture. The spatiotemporal control of DSB formation occurs within a specialized chromosomal structure characterized by sister chromatids organized into linear arrays of chromatin loops that are anchored to a proteinaceous axis. Although SPO11 and its partner proteins required for DSB formation are bound to the axis, DSBs occur preferentially within the chromatin loops, which supports the “tethered-loop/axis model” for meiotic recombination. In this mini review, we discuss insights gained from recent efforts to define and profile DSB hotspots at high resolution in eukaryotic genomes. These advances are deepening our understanding of how meiotic recombination shapes genetic diversity and genome evolution in diverse species

ASY1 acts as a dosage-dependent antagonist of telomere-led recombination and mediates crossover interference in Arabidopsis.

During meiosis, interhomolog recombination produces crossovers and noncrossovers to create genetic diversity. Meiotic recombination frequency varies at multiple scales, with high subtelomeric recombination and suppressed centromeric recombination typical in many eukaryotes. During recombination, sister chromatids are tethered as loops to a polymerized chromosome axis, which, in plants, includes the ASY1 HORMA domain protein and REC8-cohesin complexes. Using chromatin immunoprecipitation, we show an ascending telomere-to-centromere gradient of ASY1 enrichment, which correlates strongly with REC8-cohesin ChIP-seq data. We mapped crossovers genome-wide in the absence of ASY1 and observe that telomere-led recombination becomes dominant. Surprisingly, asy1/+ heterozygotes also remodel crossovers toward subtelomeric regions at the expense of the pericentromeres. Telomeric recombination increases in asy1/+ occur in distal regions where ASY1 and REC8 ChIP enrichment are lowest in wild type. In wild type, the majority of crossovers show interference, meaning that they are more widely spaced along the chromosomes than expected by chance. To measure interference, we analyzed double crossover distances, MLH1 foci, and fluorescent pollen tetrads. Interestingly, while crossover interference is normal in asy1/+, it is undetectable in asy1 mutants, indicating that ASY1 is required to mediate crossover interference. Together, this is consistent with ASY1 antagonizing telomere-led recombination and promoting spaced crossover formation along the chromosomes via interference. These findings provide insight into the role of the meiotic axis in patterning recombination frequency within plant genomes.Research was supported by grants from the European Research Council Consolidator award SynthHotSpot and Proof-of-Concept award HEIREC and BBSRC ERA-CAPs Grant BB/M004937/1

Natural Variation in TBP-ASSOCIATED FACTOR 4b Controls Meiotic Crossover and Germline Transcription in Arabidopsis.

Meiotic crossover frequency varies within genomes, which influences genetic diversity and adaptation. In turn, genetic variation within populations can act to modify crossover frequency in cis and trans. To identify genetic variation that controls meiotic crossover frequency, we screened Arabidopsis accessions using fluorescent recombination reporters. We mapped a genetic modifier of crossover frequency in Col × Bur populations of Arabidopsis to a premature stop codon within TBP-ASSOCIATED FACTOR 4b (TAF4b), which encodes a subunit of the RNA polymerase II general transcription factor TFIID. The Arabidopsis taf4b mutation is a rare variant found in the British Isles, originating in South-West Ireland. Using genetics, genomics, and immunocytology, we demonstrate a genome-wide decrease in taf4b crossovers, with strongest reduction in the sub-telomeric regions. Using RNA sequencing (RNA-seq) from purified meiocytes, we show that TAF4b expression is meiocyte enriched, whereas its paralog TAF4 is broadly expressed. Consistent with the role of TFIID in promoting gene expression, RNA-seq of wild-type and taf4b meiocytes identified widespread transcriptional changes, including in genes that regulate the meiotic cell cycle and recombination. Therefore, TAF4b duplication is associated with acquisition of meiocyte-specific expression and promotion of germline transcription, which act directly or indirectly to elevate crossovers. This identifies a novel mode of meiotic recombination control via a general transcription factor.This work was supported by a BBSRC DTP studentship (EJL), European Research Area Network for Coodinating Action in Plant Sciences/BBSRC “DeCOP” (BB/M004937/1) (CAL), a BBSRC David Phillips Fellowship (BB/L025043/1) (HG, XF), the European Research Council (CoG ‘SynthHotspot’) (AJT, CAL, IRH) and (StG ‘SexMeth’) (XF) and a Sainsbury Charitable Foundation Studentship (ARB)

DNA bending by M.EcoKI methyltransferase is coupled to nucleotide flipping

The maintenance methyltransferase M.EcoKI recognizes the bipartite DNA sequence 5′-AACNNNNNNGTGC-3′, where N is any nucleotide. M.EcoKI preferentially methylates a sequence already containing a methylated adenine at or complementary to the underlined bases in the sequence. We find that the introduction of a single-stranded gap in the middle of the non-specific spacer, of up to 4 nt in length, does not reduce the binding affinity of M.EcoKI despite the removal of non-sequence-specific contacts between the protein and the DNA phosphate backbone. Surprisingly, binding affinity is enhanced in a manner predicted by simple polymer models of DNA flexibility. However, the activity of the enzyme declines to zero once the single-stranded region reaches 4 nt in length. This indicates that the recognition of methylation of the DNA is communicated between the two methylation targets not only through the protein structure but also through the DNA structure. Furthermore, methylation recognition requires base flipping in which the bases targeted for methylation are swung out of the DNA helix into the enzyme. By using 2-aminopurine fluorescence as the base flipping probe we find that, although flipping occurs for the intact duplex, no flipping is observed upon introduction of a gap. Our data and polymer model indicate that M.EcoKI bends the non-specific spacer and that the energy stored in a double-stranded bend is utilized to force or flip out the bases. This energy is not stored in gapped duplexes. In this way, M.EcoKI can determine the methylation status of two adenine bases separated by a considerable distance in double-stranded DNA and select the required enzymatic response

Explaining the abundance of ants in lowland tropical rainforest canopies

The extraordinary abundance of ants in tropical rainforest canopies has led to speculation that numerous arboreal ant taxa feed principally as “herbivores” of plant and insect exudates. Based on nitrogen (N) isotope ratios of plants, known herbivores, arthropod predators, and ants from Amazonia and Borneo, we find that many arboreal ant species obtain little N through predation and scavenging. Microsymbionts of ants and their hemipteran trophobionts might play key roles in the nutrition of taxa specializing on N-poor exudates. For plants, the combined costs of biotic defenses and herbivory by ants and tended Hemiptera are substantial, and forest losses to insect herbivores vastly exceed current estimates

On the Government’s Protection of Citizens’ Right to Know

本文讨论的是政府对于公民知情权的保护。文章主要分为三个部分：政府保护公民知情权的必要性、政府如何来保护公民的知情权以及我国政府保护公民知情权的现状和完善建议。文章由前言、第一章、第二章、第三章和结语组成。第一章论述政府保护公民知情权的必要性。本章分为两部分：政府为什么要保护公民的知情权和为什么是由政府来承担公民知情权的保护义务。信息失灵是信息社会信息不充分和信息占有不公平的现象。信息失灵的存在是不可避免的，同时信息失灵影响到了信息社会的各个方面，造成了信息社会信息资源利用的无效率和信息社会的不公平和不便利。这在一定程度上催生了公民对于知情权利的渴求，所以政府保护公民知情权也是政府解决信息社会信...The article discusses the government’s protection on citizen’s right to know. It contains three parts: the necessities for the government to protect citizens’ right to know, how to protect the right to know, the present situation and the perfection of our government’s protection mechanisms. It consists of the preface、chapter1、chapter2、chaper3 and the conclusion. Chapter 1 describes the nec...学位：法律硕士院系专业：法学院法律系_法律硕士(JM)学号：20040817

Long-Term Effects of Metformin and Lifestyle Modification on Nonalcoholic Fatty Liver Disease Obese Adolescents

Objective. To assess the long-term effects of metformin in combination with lifestyle intervention and its association between insulin levels and the degree of steatosis at ultrasonography (US) in obese adolescents. Methods. Thirty-five postpubertal obese boys were randomized into two groups: one receiving metformin in combination with a multidisciplinary lifestyle intervention versus a placebo group, which also received the same intervention. The visceral, subcutaneous fat and degree of steatosis were measured by ultrasonography. Fasting blood samples were collected to analyze glucose, insulin, insulin resistance, and aminotransferases. Repeated ANOVA measures were used to compare changes over time and between groups, and Spearman's correlations were used to identify an association between insulin and the degree of steatosis at US. Results. There was a positive correlation between the degree of steatosis at US with insulin concentrations and HOMA-IR. Long-term therapy plus metformin significantly reduced body weight, body mass index, insulin, HOMA-IR, and visceral fat. Conclusions. Metformin was more effective than the placebo in improving clinical parameters associated with obesity and steatosis

Conceptual Design of the LHC Interaction Region Upgrade: Phase-I

The LHC is starting operation with beam. The primary goal of CERN and the LHC community is to ensure that the collider is operated efficiently and that it achieves nominal performance in the shortest term. Since several years the community has been discussing the directions for maximizing the physics reach of the LHC by upgrading the experiments, in particular ATLAS and CMS, the LHC machine and the CERN proton injector complex, in a phased approach. The first phase of the LHC interaction region upgrade was approved by Council in December 2007. This phase relies on the mature Nb-Ti superconducting magnet technology with the target of increasing the LHC luminosity to 2 to 3 10^34 cm^-2s^-1, while maximising the use of the existing infrastructure. In this report, we present the goals and the proposed conceptual solutions for the LHC IR Upgrade Phase-I which include the recommendations of the conceptual design review

Quality of life in Brazilian obese adolescents: effects of a long-term multidisciplinary lifestyle therapy

© 2009 Lofrano-Prado et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens